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FEN1 (flap structure-specific endonuclease 1)

Written2010-01L David Finger, Binghui Shen
Division of Radiation Biology, Department of Cancer Biology, City of Hope National Cancer Center Beckman Research Institute, 1500 E Duarte Road, Duarte, CA 91010-3000, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesRAD2
Alias_symbol (synonym)FEN-1
MF1
Other aliashFEN-1
HGNC (Hugo) FEN1
LocusID (NCBI) 2237
Atlas_Id 40543
Location 11q12.2  [Link to chromosome band 11q12]
Location_base_pair Starts at 61560109 and ends at 61564714 bp from pter ( according to hg19-Feb_2009)  [Mapping FEN1.png]
Fusion genes
(updated 2016)
FEN1 (11q12.2) / SULF1 (8q13.2)HS3ST4 (16p12.1) / FEN1 (11q12.2)

DNA/RNA

 
  Figure 1.
Description Spans 4561 bp; two exons; one intron (Figure 1).
Transcription Spliced transcript is 2265 bp in length. First exon is 1-351 bp and the second exon comprises 352 to 2265 bps of the spliced mRNA. The open reading frame spans 1142 base pairs (bp 373-1515).

Protein

 
  Figure 2. Structure of human FEN1.
A. Schematic of hFEN1 organization as determined by primary sequence analysis (Shen et al., 1998). The protein is divided into the N-terminal (N), Intermediate (I), C-terminal (C), and extended C-terminal regions colored in blue, green, red, and grey, respectively.
B. Structure of hFEN1 (1UL1) colored according to region. Note: electron density for portions of the I-region and the extended C-terminus were not observed (Sakurai et al., 2005).
C. Topology diagram of hFEN1 (Horton, 2008) colored according to region. Filled triangles and circles indicate structural elements that are conserved in all known FEN1s, whereas open circles and triangles indicate structural elements that vary between phage and archaeal/eukaryotic FEN1s. Yellow stars indicate the relative positions of the active site carboxylate residues that bind the requisite divalent metal ions.
D. Two-dimensional schematic of the hFEN1 structure (Grasby J, U. Sheffield, personal communication). Note: the amino terminus of hFEN1 (true for other archaeal and eukaryotic FEN1s as well) is structured and resides near the active site.
E. Schematic illustration of hFEN1 and its interaction with a double-flap substrate. The duplex DNA 3' of the cleavage site is denoted as the downstream duplex (cyan). The upstream duplex dsDNA (magenta) is 5' to the cleavage site. The 5'-ssDNA flap (brown) likely interacts with the helical arch formed by the I-region (Chapados et al., 2004; Liu et al., 2006; Devos et al., 2007; Nazarkina et al., 2008).
Description Human FEN1 is a metallonuclease comprised of 380 amino acid residues (Nazarkina et al., 2008). The protein has a nuclease core domain composed of the N, I, and C regions and an extended C-terminus (Figure 2A) (Shen et al., 1998). The extended C-terminus is dispensable for nuclease activity, but is important for protein-protein interaction with partners like PCNA and WRN (Brosh et al., 2001; Brosh et al., 2002; Zheng et al., 2005; Zheng et al., 2007; Guo et al., 2008; Nazarkina et al., 2008; Karanja and Livingston, 2009) and contains a bipartite nuclear localization signal (Qiu et al., 2001). Structural studies show that the nuclease core domain of FEN1 has a SAM-like or PIN-like fold with a mixed beta-sheet buttressed on both sides by alpha-helical structure and spanned by an arch-like structure (Figure 2B and C) (Horton, 2008). Moreover, the N and C regions form the saddle-like structure of the protein that binds dsDNA and provide the amino acid residues that bind the requisite divalent ions (Figure 2D). hFEN1 binds two divalent metal ions (Sakurai et al., 2005) and is thought to achieve phosphodiesterase activity using a 'two-metal-ion' mechanism (Yang et al., 2006; Syson et al., 2008). The C-region contains an H3tH motif and binds the downstream dsDNA of the substrate (Figure 3E). The N-region interacts with the upstream dsDNA. Notably, a hydrophobic wedge stacks on the terminal base pair of the upstream duplex closest to the active site and a cleft or pocket binds to a 3'-extrahelical nucleotide. The N and C regions are interrupted by the I-region, which forms an arch that spans the beta-sheet and the active site residues. The arch likely interacts with the 5'-ssDNA flap (Chapados et al., 2004; Liu et al., 2006; Devos et al., 2007; Nazarkina et al., 2008).
Human FEN1 is subject to post-translational modifications, which are thought to regulate hFEN1 activities in vivo (Nazarkina et al., 2008). The extended C-terminal domain can be acetylated in vitro by p300 at four lysine residues (Friedrich-Heineken et al., 2003). A mass spec analysis identified K267 and K375 of hFEN1 as in vivo sites of acetylation (Choudhary et al., 2009). Amino acid residue S187 can be phosphorylated in vitro and in vivo by CDK1-Cyclin A, which regulates the S to G2 transition. S187 phosphorylation has been shown to decrease FEN1 activity in vitro, which is consistent with the role of CDK1-Cyclin A in cell cycle regulation (Henneke et al., 2003).
Expression FEN1 is detectable in all proliferative tissues, but barely detectable in non-proliferative tissues (Warbrick et al., 1998; Kim et al., 2000). FEN1 is often overexpressed in tumor tissues (LaTulippe et al., 2002; Freedland et al., 2003; Iacobuzio-Donahue et al., 2003; Sato et al., 2003; Kim et al., 2005; Krause et al., 2005; Lam et al., 2006; Singh et al., 2008; Nikolova et al., 2009). Furthermore, cancer tissues have been reported to exhibit FEN1 promoter hypomethylation (Singh et al., 2008).
Localisation The localization of FEN1 in human cells is predominantly nuclear (Warbrick et al., 1998; Kim et al., 2000), but is also found in mitochondria (Liu et al., 2008; Szczesny et al., 2008; Kalifa et al., 2009).
 
  Figure 3. The 3'-flap directs cleavage site specificity. Using double- and single-flap synthetic substrates labeled at the 3'-terminus (indicated by the gray star), the predominant cleavage site is observed to change from the dsDNA-ssDNA junction (single flap - F(5)•T) to one nucleotide into the downstream duplex (double flap - F(5)•T3F). Single-flap substrates have a secondary cleavage site one nucleotide into the duplex that is equivalent to the cleavage site on the double flap substrate. Note: similar studies with 5'-radiolabelling show that a six-nucleotide product is formed with F(5)•T3F, whereas a 5- and 6-nucleotide product are formed with F(5)•T.
Function General biochemistry: Human FEN1 can cleave a wide variety of substrates with a 5' to 3' polarity exo- and endo-nucleolytically, albeit with widely varying levels of efficiency (Shen et al., 2005; Nazarkina et al., 2008). Regardless of substrate and cleavage efficiency, FEN1 phosphodiesterase activity results in 5'-phosphate monoester and 3'-hydroxyl products (Pickering et al., 1999; Yang et al., 2006). Consistent with its in vivo roles, hFEN1 preferentially cleaves substrates bearing a single nucleotide 3'-flap and a 5'-flap of varying length (i.e., double-flaps) (Friedrich-Heineken and Hubscher, 2004). The 3'-flap stabilizes the enzyme-substrate complex and increases subsequent first-order rates of reaction to augment "enzyme commitment" to the forward reaction (Finger et al., 2009). Furthermore, the presence of a 3'-flap on the substrate increases the cleavage site specificity, such that the enzyme cleaves exclusively at the nucleotide that lies one nucleotide into the downstream duplex (Figure 3 and 4A). With a substrate lacking a 3'-flap, the cleavage on the 5'-flap predominantly occurs at the dsDNA-ssDNA flap junction and to a lesser extent one nucleotide into the downstream duplex (Figure 3 and 4B) (Friedrich-Heineken and Hubscher, 2004; Finger et al., 2009).
Okazaki fragment maturation: Cleaves 5'-flap bifurcated nucleic acid flap structures generated by lagging-strand DNA synthesis during Okazaki fragment maturation in the nucleus (Liu et al., 2004; Garg and Burgers, 2005; Shen et al., 2005; Rossi et al., 2006; Nazarkina et al., 2008). Deletion of the FEN1 gene in mammals is embryonically lethal (Larsen et al., 2003), but deletion of its homolog in Saccharomyces cerevisiae, RAD27, is tolerated (Reagan et al., 1995). Studies in haploid yeast have shown that the deletion of RAD27 increases rates of nuclear mitotic recombination, point mutation, reversion, microsatellite instability, and frameshifts (Johnson et al., 1995; Sommers et al., 1995; Tishkoff et al., 1997; Kokoska et al., 1998; Callahan et al., 2003; Navarro et al., 2007). In a similar manner, direct-repeat recombination, chromosome loss, and interhomolog recombination were increased in rad27Δ/rad27Δ diploids (Navarro et al., 2007). In contrast to nuclear DNA, rad27Δ causes a decrease in mitochondrial direct-repeat mediated deletion and mitochondrial microsatellite instability (Kalifa et al., 2009); however, the origins of these decreases are not understood.
Long-patch base excision repair: FEN1 cleaves 5'-flap bifurcated nucleic acid structures generated during nuclear (Nazarkina et al., 2008; Robertson et al., 2009) and mitochondrial long-patch base excision repair (Liu et al., 2008; Kalifa et al., 2009; Robertson et al., 2009). Consistent with the role of FEN1 in mitochondrial long-patch base excision repair in yeast, rad27Δ mutants accumulate point mutations in mitochondrial DNA (Kalifa et al., 2009).
Telomere maintenance: FEN1 has been shown to be important for telomere stability in yeast and mammalian cells by ensuring efficient telomere replication (Parenteau and Wellinger, 1999; Parenteau and Wellinger, 2002; Saharia et al., 2008) and is essential for telomere stability in ALT-positive cells (Saharia and Stewart, 2009). Furthermore, FEN1 forms a complex with telomerase (Sampathi et al., 2009).
 
  Figure 4. The 3'-flap directs cleavage to ensure that all dsDNA product is ligatable.
A. Schematic illustration of the cleavage products of the double-flap substrate. The 3'-flap is red, the last nucleotide of the 5'-flap is purple, and the downstream duplex terminal base pair is shown in blue and orange. After cleavage, the purple and orange nucleotides are part of the ssDNA product. For the dsDNA product, the red nucleotide forms a base-pair with the blue nucleotide to create a ligatable nick.
B. In a similar manner, cleavage on the single flap substrate, which lacks the red nucleotide, occurs predominantly between the purple and orange nucleotide to create a 5-nucleotide ssDNA product and a ligatable dsDNA product. To a lesser degree, cleavage also occurs at the nucleotide one nucleotide into the downstream duplex to create a 6-nucleotide ssDNA product and a single nucleotide gap dsDNA product. Note: the substrates used in Figure 3 are static structures (i.e., they do not have the ability to equilibrate as in vivo substrates do). See following references for more detail (Kaiser et al., 1999; Kao et al., 2002; Sharma et al., 2004; Nazarkina et al., 2008).
Homology Member of the Rad2 nuclease family (i.e., close cousin to XPG, EXO1, and GEN1) (Lieber, 1997).

Mutations

Note Two FEN1 polymorphisms have been reported to be associated with an increased risk of lung cancer. The first polymorphism is c.69G>A (rs174538:G>A) and resides in the FEN1 promoter region. The second is c.4150G>T (rs4246215:G>T) and resides in the 3'-UTR of the transcript (Figure 1). Both polymorphisms are associated with decreased FEN1 expression levels (Yang et al., 2009).
DNA sequencing of DNA from tumors and tumor-derived cell lines has revealed mutations in the FEN1 gene that affect nuclease activity (Zheng et al., 2007). Furthermore, studies have shown that mice from two genetic backgrounds that are homozygous for an active site mutation known to alter enzymatic activity in vitro show an increased incidence of cancer (Zheng et al., 2007; Larsen et al., 2008).

Implicated in

Note
  
Entity Prostate cancer
Oncogenesis A gene expression profile comparing normal, primary tumor, and metastatic prostate tissue samples showed that FEN1 expression is up-regulated in primary and metastatic tumor tissue along with other DNA replication and repair genes (LaTulippe et al., 2002). The level of FEN1 expression has also been positively correlated with tumor Gleason score, and thus, tumor dedifferentiation (Lam et al., 2006). Furthermore, aggressive forms of prostate cancer as defined by the ability to form tumors in SCID mice show a five-fold or greater increase in FEN1 expression in comparison to a nontumorigenic clone (Freedland et al., 2003).
  
  
Entity Pancreatic cancer
Oncogenesis Using cDNA microarrays, a global gene expression profile of pancreatic adenocarcinoma identified FEN1 as one of 103 previously unidentified genes that were expressed at higher levels in comparison to normal tissue (Iacobuzio-Donahue et al., 2003).
  
  
Entity Gastric cancer
Oncogenesis Using cDNA microarrays and semi-quantitative RT-PCR, FEN1 was shown to be up-regulated in comparison to normal tissue (Kim et al., 2005). Furthermore, using a cancer profiling array and immunohistochemistry, FEN1 was also shown to be up-regulated in stomach cancer (Singh et al., 2008).
  
  
Entity Lung cancer
Oncogenesis FEN1 levels were elevated in small cell and non-small-cell cancers in comparison to normal lung controls (Sato et al., 2003). Furthermore, using a cancer profiling array and immunohistochemistry, FEN1 was also shown to be up-regulated at the mRNA and protein level in lung cancer (Singh et al., 2008; Nikolova et al., 2009).
  
  
Entity Brain cancer
Oncogenesis Gene expression patterns in neuroblastomas were analyzed using microarrays and confirmed by RT-PCR to show that neuroblastomas with unfavorable clinical outcome express FEN1 at levels 2.7-fold higher than neuroblastomas detected by mass screening (Krause et al., 2005), thereby implying that FEN1 expression level in neuroblastoma could be diagnostic of clinical outcome. Futhermore, FEN1 expression levels are higher in glioblastoma multiforme, primary astrocytoma, anaplastic astrocytoma, and oligoastrocytoma as determined by Western blotting (Nikolova et al., 2009).
  
  
Entity Breast cancer
Oncogenesis A cancer profiling array and immunohistochemistry showed increased levels of FEN1 expression at the mRNA and protein levels. In addition, increased expression is likely due to promoter hypomethylation. Furthermore, this study showed that increased FEN1 expression is positively correlated with advanced or higher grace breast tumors (Singh et al., 2008).
  
  
Entity Testicular cancer
Oncogenesis Western blotting analysis showed increased levels of FEN1 in 14 out of the 17 seminomas (Nikolova et al., 2009).
  
  
Entity Other cancers
Oncogenesis Overexpression of FEN1 at the mRNA level has also been detected in uterine, colon, ovarian, and kidney cancer tissues (Singh et al., 2008). In summary, expression of FEN1 is commonly increased to facilitate cell proliferation in cancer cells due to the pivotal role of FEN1 in DNA replication. However, partial or complete loss of function is also known to facilitate the development of cancer by causing genomic instability in eukaryotes (Navarro et al., 2007; Zheng et al., 2007; Larsen et al., 2008).
  

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PMID 10211123
 
Functional FEN1 polymorphisms are associated with DNA damage levels and lung cancer risk.
Yang M, Guo H, Wu C, He Y, Yu D, Zhou L, Wang F, Xu J, Tan W, Wang G, Shen B, Yuan J, Wu T, Lin D.
Hum Mutat. 2009 Sep;30(9):1320-8.
PMID 19618370
 
Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity.
Yang W, Lee JY, Nowotny M.
Mol Cell. 2006 Apr 7;22(1):5-13. (REVIEW)
PMID 16600865
 
Fen1 mutations result in autoimmunity, chronic inflammation and cancers.
Zheng L, Dai H, Zhou M, Li M, Singh P, Qiu J, Tsark W, Huang Q, Kernstine K, Zhang X, Lin D, Shen B.
Nat Med. 2007 Jul;13(7):812-9. Epub 2007 Jun 24.
PMID 17589521
 
Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks.
Zheng L, Zhou M, Chai Q, Parrish J, Xue D, Patrick SM, Turchi JJ, Yannone SM, Chen D, Shen B.
EMBO Rep. 2005 Jan;6(1):83-9.
PMID 15592449
 

Citation

This paper should be referenced as such :
Finger, LD ; Shen, B
FEN1 (flap structure-specific endonuclease 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):955-961.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/FEN1ID40543ch11q12.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(5;11)(q35;q12) NSD1/FEN1


External links

Nomenclature
HGNC (Hugo)FEN1   3650
Cards
AtlasFEN1ID40543ch11q12
Entrez_Gene (NCBI)FEN1  2237  flap structure-specific endonuclease 1
AliasesFEN-1; MF1; RAD2
GeneCards (Weizmann)FEN1
Ensembl hg19 (Hinxton)ENSG00000168496 [Gene_View]  chr11:61560109-61564714 [Contig_View]  FEN1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000168496 [Gene_View]  chr11:61560109-61564714 [Contig_View]  FEN1 [Vega]
ICGC DataPortalENSG00000168496
TCGA cBioPortalFEN1
AceView (NCBI)FEN1
Genatlas (Paris)FEN1
WikiGenes2237
SOURCE (Princeton)FEN1
Genetics Home Reference (NIH)FEN1
Genomic and cartography
GoldenPath hg19 (UCSC)FEN1  -     chr11:61560109-61564714 +  11q12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)FEN1  -     11q12   [Description]    (hg38-Dec_2013)
EnsemblFEN1 - 11q12 [CytoView hg19]  FEN1 - 11q12 [CytoView hg38]
Mapping of homologs : NCBIFEN1 [Mapview hg19]  FEN1 [Mapview hg38]
OMIM600393   
Gene and transcription
Genbank (Entrez)AK301743 AK312761 BC000323 BM450370 BP244711
RefSeq transcript (Entrez)NM_004111
RefSeq genomic (Entrez)NC_000011 NC_018922 NT_167190 NW_004929380
Consensus coding sequences : CCDS (NCBI)FEN1
Cluster EST : UnigeneHs.409065 [ NCBI ]
CGAP (NCI)Hs.409065
Alternative Splicing GalleryENSG00000168496
Gene ExpressionFEN1 [ NCBI-GEO ]   FEN1 [ EBI - ARRAY_EXPRESS ]   FEN1 [ SEEK ]   FEN1 [ MEM ]
Gene Expression Viewer (FireBrowse)FEN1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2237
GTEX Portal (Tissue expression)FEN1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP39748   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP39748  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP39748
Splice isoforms : SwissVarP39748
PhosPhoSitePlusP39748
Domaine pattern : Prosite (Expaxy)XPG_1 (PS00841)    XPG_2 (PS00842)   
Domains : Interpro (EBI)5-3_exonuclease_C    Flap_endonuc    HhH2    PIN_domain-like    XPG-I_dom    XPG/Rad2    XPG_CS    XPG_DNA_repair_N   
Domain families : Pfam (Sanger)XPG_I (PF00867)    XPG_N (PF00752)   
Domain families : Pfam (NCBI)pfam00867    pfam00752   
Domain families : Smart (EMBL)HhH2 (SM00279)  XPGI (SM00484)  XPGN (SM00485)  
Conserved Domain (NCBI)FEN1
DMDM Disease mutations2237
Blocks (Seattle)FEN1
PDB (SRS)1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
PDB (PDBSum)1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
PDB (IMB)1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
PDB (RSDB)1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
Structural Biology KnowledgeBase1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
SCOP (Structural Classification of Proteins)1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
CATH (Classification of proteins structures)1U7B    1UL1    3Q8K    3Q8L    3Q8M    3UVU   
SuperfamilyP39748
Human Protein AtlasENSG00000168496
Peptide AtlasP39748
HPRD02670
IPIIPI00026215   IPI01009939   
Protein Interaction databases
DIP (DOE-UCLA)P39748
IntAct (EBI)P39748
FunCoupENSG00000168496
BioGRIDFEN1
STRING (EMBL)FEN1
ZODIACFEN1
Ontologies - Pathways
QuickGOP39748
Ontology : AmiGOtelomere maintenance via recombination  double-strand break repair via homologous recombination  nuclear chromosome, telomeric region  nuclear chromosome, telomeric region  DNA binding  damaged DNA binding  double-stranded DNA binding  endonuclease activity  RNA-DNA hybrid ribonuclease activity  exonuclease activity  protein binding  nucleus  nucleoplasm  nucleolus  mitochondrion  plasma membrane  DNA replication  DNA repair  double-strand break repair  memory  double-stranded DNA exodeoxyribonuclease activity  5'-3' exonuclease activity  UV protection  membrane  5'-flap endonuclease activity  5'-flap endonuclease activity  5'-flap endonuclease activity  DNA replication, removal of RNA primer  protein complex  metal ion binding  nucleic acid phosphodiester bond hydrolysis  nucleic acid phosphodiester bond hydrolysis  RNA phosphodiester bond hydrolysis, endonucleolytic  
Ontology : EGO-EBItelomere maintenance via recombination  double-strand break repair via homologous recombination  nuclear chromosome, telomeric region  nuclear chromosome, telomeric region  DNA binding  damaged DNA binding  double-stranded DNA binding  endonuclease activity  RNA-DNA hybrid ribonuclease activity  exonuclease activity  protein binding  nucleus  nucleoplasm  nucleolus  mitochondrion  plasma membrane  DNA replication  DNA repair  double-strand break repair  memory  double-stranded DNA exodeoxyribonuclease activity  5'-3' exonuclease activity  UV protection  membrane  5'-flap endonuclease activity  5'-flap endonuclease activity  5'-flap endonuclease activity  DNA replication, removal of RNA primer  protein complex  metal ion binding  nucleic acid phosphodiester bond hydrolysis  nucleic acid phosphodiester bond hydrolysis  RNA phosphodiester bond hydrolysis, endonucleolytic  
Pathways : KEGGDNA replication    Base excision repair    Non-homologous end-joining   
REACTOMEP39748 [protein]
REACTOME Pathways110362 [pathway]   162594 [pathway]   174437 [pathway]   5651801 [pathway]   5685939 [pathway]   69166 [pathway]   
NDEx NetworkFEN1
Atlas of Cancer Signalling NetworkFEN1
Wikipedia pathwaysFEN1
Orthology - Evolution
OrthoDB2237
GeneTree (enSembl)ENSG00000168496
Phylogenetic Trees/Animal Genes : TreeFamFEN1
HOVERGENP39748
HOGENOMP39748
Homologs : HomoloGeneFEN1
Homology/Alignments : Family Browser (UCSC)FEN1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFEN1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FEN1
dbVarFEN1
ClinVarFEN1
1000_GenomesFEN1 
Exome Variant ServerFEN1
ExAC (Exome Aggregation Consortium)FEN1 (select the gene name)
Genetic variants : HAPMAP2237
Genomic Variants (DGV)FEN1 [DGVbeta]
DECIPHER (Syndromes)11:61560109-61564714  ENSG00000168496
CONAN: Copy Number AnalysisFEN1 
Mutations
ICGC Data PortalFEN1 
TCGA Data PortalFEN1 
Broad Tumor PortalFEN1
OASIS PortalFEN1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFEN1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDFEN1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch FEN1
DgiDB (Drug Gene Interaction Database)FEN1
DoCM (Curated mutations)FEN1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FEN1 (select a term)
intoGenFEN1
NCG5 (London)FEN1
Cancer3DFEN1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600393   
Orphanet
MedgenFEN1
Genetic Testing Registry FEN1
NextProtP39748 [Medical]
TSGene2237
GENETestsFEN1
Huge Navigator FEN1 [HugePedia]
snp3D : Map Gene to Disease2237
BioCentury BCIQFEN1
ClinGenFEN1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2237
Chemical/Pharm GKB GenePA28090
Clinical trialFEN1
Miscellaneous
canSAR (ICR)FEN1 (select the gene name)
Probes
Litterature
PubMed168 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFEN1
EVEXFEN1
GoPubMedFEN1
iHOPFEN1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:40:45 CET 2017

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